Project Summary One in five children in the US grows up in poverty. These children face high risk for psychopathology, which often lasts a lifetime and perpetuates low socioeconomic status. Thus, poverty and its sequelae represent a major public health problem. Poor children often experience greater chronic stress, which may allow poverty to become biologically embedded by altering brain and hypothalamic-pituitary-adrenal (HPA) axis function. By examining teens growing up with poverty-related stressors, the study will explicate the RDoC Sustained Threat Construct in response to RFA-MH-14-050. Little is known about how poverty impacts underlying biological mechanisms and gives rise to symptoms, such as anxiety and depression. This lack of knowledge hinders efforts to develop interventions targeting mechanisms linking poverty and psychopathology. Our objective is to better understand how poverty affects biology during development and leads to psychopathology. The central hypothesis is that poverty increases the occurrence of four types of stressors (exposure to danger, family conflict, residential instability, neglect), which leads to HPA axis dysregulation, increased amygdala activation and less mature regulatory connections from the ventromedial prefrontal cortex to the amygdala; extended exposure to poverty-related stressors leads to a protracted period when the HPA axis and amygdala are hyper- active, resulting in a systemic shift toward greater allocation of neural and cognitive resources to negative events and more negative affect, including anxiety and depression symptoms, as measured with self- and parental-reports. Teens will be assessed from The Fragile Families and Child Wellbeing Study (FFCWS), an ongoing study of children born to predominantly low-income families. Attributes of the FFCWS are: 1) children were assessed at birth, 1, 3, 5 and 9 years and will be assessed at 15; 2) the sample is representative of children born in their city and, thus, unlike almost all other brain imaging research, findings are generalizable; 3) Although the sample contains high levels of poverty, a full range of incomes are represented allowing for comparisons; and 4) Youth are now entering mid-adolescence - a period of heightened risk for psychopathology. When subjects are 15, affective function will be assessed at four levels of analysis: 1) brain (with functional MRI to assess activation and connectivity in response to emotional faces and with diffusion tensor imaging to measure structural connectivity); 2) HPA axis (by measuring cortisol in response to a stressor and DHEA); 3) behavior (using an attention bias measure); and 4) self- and parent-report measures of negative affect with follow-up at age 17. Developmental history from FFCWS (economic conditions, symptoms, parenting) will be mapped onto affective function at these four levels of analysis. By leveraging the FFCWS, the team is well positioned to conduct research that integrates experience across childhood with neurobiological and psychological data to better elucidate a major path to psychopathology.